Caspases play important roles in apoptosis and cellular states
Apoptosis is a programmed, cell-autonomous death process. It plays important roles in a variety of physiological and pathological events1 , ranging from normal fetal development to diseases, such as cancer2 , organ failure and neurodegenerative diseases.
During apoptosis, caspases execute the disassembly of the cellular components by proteolytic cleavage of a variety of substrates, such as poly-(ADP ribose) polymerase (PARP)3 , DNA-dependent protein kinase (DNA-PK), topoisomerases, and protein kinase C (PKC)δ. 4
Caspases are a family
of 12 cysteine proteases
Caspases are popularly studied for driving cell death. They are initially produced as inactive monomeric procaspases that require dimerization and often cleavage for activation. Caspases are broadly classified by their known roles in apoptosis (caspases 2, 3, 6, 7, 8, and 9 in mammals), and in other cellular states such as in inflammation (caspases 1, 4, 5, 12 in humans and caspases 1, 11, and 12 in mice). Further, the caspases have been sub-classified based on their modes of action as either initiator caspases (caspases, 2, 8, 9, 10) or executioner caspases (caspases 3, 6, 7).
Initiator caspases are said to cleave inactive procaspase dimers that in turn act on executioner caspases (caspases 3, 6 and 7). Once activated, a single executioner caspase can cleave and activate other executioner caspases, ultimately leading to apoptotic destruction of the cell.
From proteomic characterization of caspase substrates, a number of substrate sequences that caspases cleave have been identified with high degrees of specificities, thereby indicating specialized functions for each caspase in cell biology.
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- Lazebnik, Y. A. et al. Nature 371, 346-347 (1994).
- Villa, P. et al. Trends Biochem. Sci. 22, 388-393 (1997).